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C Benvenuti

Publications and source records attributed to C Benvenuti.

At least 37 records · Page 2Linked to original sources

[Wearable Baxter-Novacor mechanical ventricular assistance].

Progressive technological developments have permitted clinical use of the wearable Baxter-Novacor left ventricular assist system. The system allows total bypass of the left ventricular function, and recovery of and adequate circulation in patients in cardiogenic shock. Since the first clinical use, in March 1993, eight patients about to die have been supported with a cardiac transplantation. This experience suggests that an an acceptable answer to the problem of organ shortage is now available.

Adolescent↗

Absorption of oral lornoxicam in healthy volunteers using a granular formulation in comparison with standard tablets.

The bioavailability of lornoxicam (CAS 70374-39-9), a novel highly potent anti-inflammatory and analgesic agent, was studied in healthy volunteers after single doses of a new oral formulation (8 mg granules) in comparison to tablets (8 mg). Eighteen healthy volunteers (6 males and 12 females) with a mean age of 29.4 were given a single 8 mg dose of each formulation in an open, cross-over study, with randomised sequences. Lornoxicam plasma levels were determined by an HPLC method. Cmax, AUC0-infinity and t 1/2 beta values were similar for both the granules and tablets, but tmax and lag time values after lornoxicam granules were significantly shorter than after the tablets. During the study, no side-effects were noted with either of the formulations studied. Therefore this study showed that lornoxicam granular formulation had a faster absorption than tablets even though the two formulations can be considered bioequivalent.

Adolescent↗

Sympathetic stimulation overrides flow-mediated endothelium-dependent epicardial coronary vasodilation in transplant patients.

BACKGROUND: Abnormal coronary vasomotor responses have been described in transplant patients. The aim of this study was to evaluate the graft epicardial vasomotor responses to different stimuli that increase coronary blood flow. METHODS AND RESULTS: Twelve heart transplant recipients with angiographically normal epicardial coronary arteries were compared 2.7 +/- 1.2 months after surgery with 6 control subjects. Coronary flow velocity was measured with a guidewire Doppler. Coronary diameter changes of the proximal and midportion of the left anterior descending coronary artery were assessed by quantitative coronary angiography during rapid atrial pacing, cold pressor test, supine exercise, and subselective infusion of papaverine and after intracoronary injection of linsidomine (SIN-1). Catecholamine plasmatic levels were determined at the different stages of the protocol. In 6 other transplant patients, a cold pressor test was performed before and after intracoronary infusion of phentolamine (10 micrograms.kg-1.min-1). Coronary flow velocity increased significantly in both groups during each phase of the protocol. In control subjects, dilation was observed in response to atrial pacing (8.7 +/- 7.6%; P < .05), CPT (8.8 +/- 2.3%; P < .01), exercise (14.5 +/- 9.4%; P < .001), and papaverine infusion (14.2 +/- 6.1%; P < .001) and after injection of SIN-1 (26.8 +/- 11.9%; P < .001). In transplant patients, similar dilation was observed during atrial pacing (8.2 +/- 8.3%; P < .05) and papaverine infusion (14.6 +/- 7.8%; P < .001) and after SIN-1 (25.8 +/- 10.8%; P < .001). CPT and exercise caused slight constriction (-3.5 +/- 4.5% and -2.7 +/- 10.5%, respectively; both P < .001 versus control subjects). Norepinephrine plasmatic levels increased in both groups during CPT and exercise. Slight constriction during the cold pressor test (-4.5 +/- 9.6%) changed to dilation (6.8 +/- 7.0%) after alpha-blockade with phentolamine (P < .001). CONCLUSIONS: These results show that flow-mediated, endothelium-dependent vasodilation is preserved early after trans-plantation. Sympathetic stimulation, which overrides the endothelium-dependent mechanism, can be related to hypersensitivity to catecholamines due to denervation.

Adrenergic alpha-Antagonists↗

Increased serum nitrate concentration in cardiac transplant patients. A marker for acute allograft cellular rejection.

The purpose of the present study was to investigate whether nitrate serum level, reflecting total body production of nitric oxide in vivo, could serve as a noninvasive marker for acute human cardiac rejection. Serum nitrate concentration was determined by an enzymatic method. During routine right ventricular endomyocardial biopsies in 59 recipients, 145 tissue samples were obtained. Two groups of biopsy specimen were considered on the basis of posttransplant delay: group 1, < or = 90 days (n=47; 12-90 days); and group 2, >90 days (n=98; 3-81 months). All patients had normal ventricular systolic function on the day of biopsy and none had evidence of infection. Rejection grade correlated closely with serum nitrate concentration (P<0.001). In both groups, nitrate serum concentrations differed significantly (P<0.001) among cases without rejection, those with mild ongoing rejection (grade 1A/1B), and those with focal or diffuse aggressive infiltrates (grade 2 or higher). A cutoff value of 20 micromol/L, was determined that was positively predictive for grade 2 or higher rejection in 62% cases of early episodes of rejection and in 68% cases of late rejection. Conversely, a serum nitrate level below 20 micromol/L was negatively predictive in 97% and 94% of early and late cases, respectively. We conclude that the acute rejection process of the human transplanted heart is accompanied by a significant increase in serum nitrate level, reflecting increased nitric oxide production during the immune response. Because of its high negative predictive value, irrespective of the posttransplantation delay, nitrate serum determination may have clinical utility in the noninvasive monitoring of the cardiac transplant patient and could also add important information to endomyocardial biopsy analysis for treatment decision making.

Graft Rejection↗

Mechanical bridge to transplantation: when is too early? When is too late?

BACKGROUND: Optimal timing of implantation of a mechanical circulatory support system in the treatment of acute cardiogenic shock is still unsettled. The issue has been addressed in a retrospective analysis of a group of 98 patients in cardiogenic shock refractory to medical therapy who were candidates for cardiac transplantation, admitted from 1987 to 1994. METHODS: The treatment included reinforced inotropic support by addition of phosphodiesterase inhibitors to sympathomimetic agents. The patients who did not improve were immediately brought to the operating room for mechanical circulatory support system implantation. RESULTS: The overall survival in the group of 28 patients selected for mechanical bridge is 50%. No predictive factors of death or multiorgan failure while on the device could be identified, suggesting a lack of contraindications to mechanical circulatory support system implantation. CONCLUSIONS: The high death rate in patients maintained on medical therapy because of initial improvement as they are awaiting transplantation suggests the benefit of a rapid semielective implantation of an intracorporeal device.

Adult↗

Serum and urinary nitrate levels in liver cirrhosis: endotoxemia, renal function and hyperdynamic circulation.

BACKGROUND/AIMS: The relationship between nitric oxide production, endotoxemia, renal function and hyperdynamic circulatory syndrome has not been yet investigated in patients with cirrhosis. METHODS: Serum and urine nitrate, endotoxemia and cardiac index were measured in 59 patients with cirrhosis. RESULTS: Patients with a tense ascites had higher serum nitrate levels than healthy control subjects (39 +/- 7 vs 19 +/- 4 mumol/l, p < 0.01). Patients with mild ascites and without ascites had normal values of nitrate levels. In the group of patients not treated with diuretics (n = 38), creatinine and nitrate clearances were lower in ascitic patients than in nonascitic patients (respectively 0.82 +/- 0.12 vs 1.48 +/- 0.32 ml/s, p < 0.02 and 0.30 +/- 0.07 vs 2.89 +/- 2.04 ml/s, p < 0.05). Endotoxin levels were higher in patients with cirrhosis than in control subjects and paralleled the severity of liver failure (Child A/B/C vs control subjects: 0.056 +/- 0.014/0.064 +/- 0.005/ 0.090 +/- 0.008 vs 0.027 +/- 0.005 Endotoxin Units/ml, p < 0.001). Serum nitrate levels did not correlate with endotoxemia (r = -0.110). On the other hand, levels of orosomucoid, a protein synthesized by the liver in response to a stimulation by cytokines correlated with those of nitrate (respectively r = 0.343, p < 0.01). Hemoglobin levels were negatively correlated with serum nitrate levels (r = -0.328 p < 0.02). Cardiac index was higher in patients than in control subjects and paralleled the degree of liver failure (Child A/B/C vs control subjects: 3.60 +/- 0.25/ 4.10 +/- 0.19/4.47 +/- 0.25 vs 3.15 +/- 0.12 l.min.m2, p < 0.001). Cardiac index did not correlate with serum nitrate levels, urine nitrate excretion and endotoxemia. CONCLUSIONS: Renal impairment accounts for the increased levels of serum nitrate in ascitic patients. A stimulation of nitric oxide production by cytokines may occur but endotoxemia is not involved in such a mechanism. Anemia has a role in nitric oxide activity. Nitric oxide generation assessed by nitrate in serum and urine does not seem to participate in the hyperdynamic circulatory syndrome in patients with cirrhosis.

Analysis of Variance↗

[Orthotopic cardiac transplantation with caval anastomosis: a comparative randomized study with standard procedure in 81 cases].

Complete resection of the right atrium with conservation of a strip of left atrium around the 4 pulmonary veins followed by direct anastomosis on the vena cava has recently been proposed as an alternative to the standard orthotopic cardiac transplantation described by Shumway and Lower. In order to determine whether this "anatomical" transplantation should now be considered to be the procedure of choice, a prospective randomised study was undertaken in 1991 including 78 patients undergoing 81 cardiac transplantations by one of the two techniques: gr. I: classical transplantation (n = 40), gr. II: "anatomical" transplantation (n = 41). The groups were comparable in age, sex, weight, nature of the underlying cardiac disease and clinical status at the time of transplantation. Similarly, the parameters of the donors were comparable with respect to age, sex, weight and dosage of inotropic drugs at the time of explantation. All patients came of cardiopulmonary bypass with comparable ischaemia time of the graft (gr. I: 136 +/- 46 min; gr. II: 138 +/- 51 min). Immediate return to sinus rhythm occurred in 20 cases in gr. I and 36 cases in gr. II. Atrial arrhythmia persisted in 5 cases in gr. I but in no cases of gr. II. These differences were very significant (p < 0.001). There were 13 early deaths in gr. I and 8 in gr. II. Doppler echocardiography was performed two to three months after transplantation. The right atrial surface was significantly decreased in gr. II (18 +/- 4.7 cm2) compared with gr. I (24 +/- 7 cm2): the same difference was observed for the left atrium (gr. I: 24 +/- 4.5 cm2; gr. II: 20 +/- 5 cm2), p = 0.001. Tricuspid regurgitation was observed in 82% of patients in gr. I compared with 57% in gr. II (p < 0.005). Exercise stress tests during the same period showed no difference in peak oxygen consumption between the groups. Holter ECG monitoring led to permanent pacing in 2 patients of gr. I (5%). The technical simplicity and reduction of postoperative morbidity, especially with respect to arrhythmias, suggest an advantage with the "anatomical" technique considering the lack of surgical complications.

Adult↗

[Wearable mechanical ventricular support].

Progressive technological developments have permitted clinical use of the wearable Baxter-Novacor left ventricular assist system. The system allows total bypass of the left ventricular function, and recovery of an adequate circulation in patients about in cardiogenic shock. Since the first clinical use, in March 1993, six patients about to die have been supported with a cardiac transplantation. This experience suggests that an acceptable answer to the problem of organ shortage is non available.

Assisted Circulation↗

Coronary artery response to cold-pressor test is impaired early after operation in heart transplant recipients.

OBJECTIVES: The aim of the present study was to evaluate the coronary vasomotor response to the cold-pressor test within 3 months after heart transplantation. BACKGROUND: Normal epicardial coronary arteries dilate in response to sympathetic stimulation evoked by the cold-pressor test. In transplant recipients, abnormal coronary vasomotion has been described shortly after operation. METHODS: Fourteen heart transplant recipients were compared 52 +/- 15 days (mean +/- SD) after operation with 10 control subjects. All had angiographically normal epicardial coronary arteries. Coronary blood flow velocity was measured with a Doppler catheter placed in the proximal left anterior descending coronary artery. Four segments in each patient were analyzed by quantitative coronary angiography to assess the diameter changes during the cold-pressor test and after intracoronary injection of isosorbide dinitrate. RESULTS: Coronary flow velocity increased similarly during the cold-pressor test in control subjects and in transplant recipients, from 7.5 +/- 2.3 to 11.0 +/- 3.9 cm/s and from 10.3 +/- 3.2 to 13.7 +/- 4.8 cm/s (both p < 0.01). In control subjects, 39 of 40 segments analyzed dilated during the cold-pressor test. In transplant recipients, 48 of 56 segments analyzed did not change or constricted. The mean epicardial coronary diameter increased significantly during the cold-pressor test in control subjects (+13 +/- 6%, p < 0.001), whereas it did not change significantly in transplant recipients (-2 +/- 9%, p = NS). In transplant recipients, isosorbide dinitrate elicited coronary vasodilation similar to that in control subjects. CONCLUSIONS: These data indicate that in human transplanted denervated hearts, coronary vasodilation in response to sympathetic stimulation by cold exposure is impaired shortly after operation.

Adult↗

Orthotopic cardiac transplantation with direct caval anastomosis: is it the optimal procedure?

Total excision of the right atrium with a minimal cuff of left atrium remaining around the four pulmonary veins, followed by direct anastomoses on venae cavae, has been proposed as an alternative to the standard procedure described by Shumway and Lower for orthotopic cardiac transplantation. To investigate whether this "anatomic" transplantation should be proposed as the optimal procedure, we prospectively randomized 78 patients having 81 procedures since 1991 into two groups: group I, standard transplantation (n = 40), and group II, "anatomic" transplantation (n = 41). The two groups were statistically similar in recipient age, sex, weight, disease, and status at the time of transplantation. Also similar were donor age, sex, weight, and drug dependency at the time of harvesting. All patients could be weaned from cardiopulmonary bypass with comparable graft ischemic times (group I, 136 +/- 46 minutes; group II, 138 +/- 51 minutes). Immediate recovery of sinus rhythm occurred in 20 cases of group I and 36 cases of group II. Delayed recovery of sinus rhythm in the first postoperative week occurred in 15 cases of group I and 5 cases of group II. Persistence of atrial arrhythmia occurred in 5 cases of group I and never in group II. These differences were highly significant (p < 0.001). Postoperative hemodynamics showed a higher cardiac index at day 1 in group II (4.12 +/- 0.85 L/min per square meter) than in group I (3.77 +/- 0.65 L/min per square meter) (p = 0.04). There were 13 early deaths in group I and 8 early deaths in group II. One death in group I was related to an acute atrioventricular block at 3 weeks with no evidence of cardiac rejection at histologic examination. Two patients in group I (5%) required definitive pacemaker implantation for prolonged sinus node dysfunction. Echocardiographic and Doppler studies of survivors have been performed 2 to 3 months after transplantation. Right atrial area was significantly reduced (p < 0.01) in group II (18 +/- 4.7 cm2) versus group I (24 +/- 7 cm2), as was left atrial area (group I, 24 +/- 4.5 cm2; group II, 20 +/- 5 cm2) (p = 0.01). Mild tricuspid regurgitation was observed in 82% of group I patients versus 57% of group II patients (p < 0.05), inasmuch as mitral regurgitation was comparable (71% in group I, 67% in group II).(ABSTRACT TRUNCATED AT 400 WORDS)

Anastomosis, Surgical↗

The pharmacokinetics of teniloxazine in healthy subjects and patients with hepatic cirrhosis.

The single-dose and steady-state pharmacokinetics of teniloxazine, an investigational drug with antidepressant and anti-anoxic properties, were compared in 12 healthy volunteers and 12 cirrhotic patients, following oral administration of 80 mg teniloxazine maleate every 12 h for 7 days. In healthy volunteers, an increase in oral clearance, CLo (from a mean (s.d.) value of 14.6 (3.9) to 18.0 (6.6) ml min-1 kg-1; mean % ratio between the two values (95% CI), 123 (94-151)) and a significant shortening of t 1/2 (from 6.2 (2.7) to 4.8 (1.4) h; mean % ratio (95% CI), 78 (58-98)) were observed upon repeated administration, suggesting autoinduction of teniloxazine metabolism. In cirrhotic patients, the pharmacokinetic parameters of teniloxazine remained essentially invariant with time. Compared with normal subjects, CLo was about halved in cirrhotic patients, whereas t 1/2 was more than doubled. As a consequence of these modifications, the multiple-dose regimen resulted in a two-fold mean drug accumulation in cirrhotic patients, compared with virtually no accumulation in healthy volunteers. Although no adverse events were noted in either study group, it is suggested that maintenance doses for patients with liver dysfunction should initially be at the lower end of the therapeutic range.

Administration, Oral↗

Early impairment of acetylcholine-induced endothelium-dependent coronary vasodilation is not predictive of secondary graft atherosclerosis.

STUDY OBJECTIVE: To test the hypothesis that the magnitude of early constriction of coronary arteries to acetylcholine might be a useful predictor of secondary graft atherosclerosis. DESIGN: The responses of epicardial coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8)M to 10(-5)M) were compared in 7 control subjects and in 18 patients who had undergone transplants within 2 months after surgery. MEASUREMENTS AND RESULTS: Vessel dimensions (percent basal diameter) were measured by quantitative angiography. Follow-up at 1 year showed angiographically normal coronary arteries in 12 patients (group 1) and coronary atherosclerosis in 6 patients (group 2). In control subjects, acetylcholine induced a dose-dependent dilation from 10(-8)M to 10(-6)M. No significant variation was observed at 10(-5)M. In patients with transplants early after surgery, diameters did not vary significantly from base at 10(-8)M in either group and constricted significantly at higher concentrations. Vasodilator responses to intracoronary isosorbide dinitrate were similar in both groups with transplants early after surgery, and at 1 year in group 1, but significantly lower than in control subjects. CONCLUSIONS: In patients who had undergone transplants, acetylcholine-induced endothelium-dependent coronary artery dilation is similarly impaired early after surgery (within 2 months) in patients with and without coronary atherosclerosis at 1-year follow-up. Thus, response to acetylcholine is not a predictor of secondary atherosclerosis in patients with heart transplants.

Acetylcholine↗

Oxatomide reduces inflammatory events induced by allergen-specific conjunctival challenge.

BACKGROUND: Allergen-specific conjunctival challenge is a safe and reproducible experimental model to evaluate effectiveness and possible mechanism(s) of action of drugs employed in the treatment of allergic diseases. OBJECTIVE: The protective effect of oxatomide on inflammatory changes that follow allergen-specific conjunctival challenge was assessed in 20 patients with rhinoconjunctivitis due to Parietaria judaica in a double-blind study. METHODS: After a screening allergen-specific conjunctival challenge, patients were randomized into two treatment groups, each being given oxatomide (oral tablets) at 60 mg daily or matching placebo for seven days during off-pollen season. Clinical evaluation, cytologic assessment (number of inflammatory cells and ICAM-1 expression on epithelial cells) were assessed at baseline, 30 minutes, 6 hours, and 24 hours after allergen-specific conjunctival challenge, before and after treatment. In addition, electrocardiograms were obtained before and after treatment. RESULTS: Early phase reaction clinical events as well as total numbers of inflammatory cells were significantly reduced by oxatomide compared with placebo. Late phase reaction clinical events as well as total numbers of inflammatory cells were significantly reduced by oxatomide compared with placebo. ICAM-1 expression was significantly reduced by oxatomide in early phase reactions and late phase reactions compared with placebo. No pathologic cardiac events were detected in any subject. CONCLUSIONS: Oxatomide has a protective effect on clinical and cellular early phase reactions and late phase reactions (including ICAM-1 expression on epithelium) induced by allergen-specific conjunctival challenge and is safe and well tolerated.

Allergens↗

[What are the criteria of priority for the patient to be accepted on the waiting list for cardiac transplantation?].

The limited resources (in grafts, human and financial resources) incited the authors to carry out a prospective assessment of the value of assessing adrenergic function (scintigraphy with meta- iodo- benzyl guanidine, MIBG) for the procedure of inscription on the waiting list of patients with cardiac failure awaiting cardiac transplantation. The study was undertaken from October 1988 to October 1992. Seventy-eight candidates for transplantation were included in the study. Forty-six patients with a MIBG cardiothoracic ratio less than 120% were placed on the waiting list. In July 1993, 35 had undergone transplantation after a 5 months delay. Four patients are still awaiting transplantation and 7 died whilst on the waiting list. Thirty two with a MIBG cardiothoracic ratio greater than 120% were treated medically: in 14 cases (43%) this decision was reviewed after 17 +/- 12 months. The clinical course was stable in the other 18 patients with a follow-up of 46 +/- 18 months (range: 12-72 months). In all, the results of this study show that a procedure of selection for inscription on the waiting list of patients with cardiac failure judged to be good candidates for transplantation based on the value of the MIBG cardiothoracic ratio allows deferrement of inscription of patients at least risk without changing the chances of survival in the whole population group within a 2 year period.

3-Iodobenzylguanidine↗

[Cardiac transplantation; results after 5 years].

After cardiac transplantation, long-term results were assessed in a group of 46 patients who survived more than 5 years after surgery. They were the survivors (50%) of a group of 92 patients who underwent transplantation before January 1990. On January 1995, mean follow-up was 82 +/- 14 months. Quality of life was estimated satisfactory (mean score 8.4 +/- 2); 60% of the patients were active; 89% were class NYHA I or II. Nevertheless, several problems have been identified: rise in body weight for all, over 10 kg in 31%; hypertension, renal failure, considered to be severe (serum creatinine > 250 micrograms/l) in 26%, diabetes in 13%, osteoarthropathy in 33%, cancer in 6%, and, above all, chronic alteration of the coronary arterial bed in 53% of the patients. These problems reflect the immunological conflict and complications of immuno-suppression.

Adolescent↗

[Nationwide drug surveillance project on slow-release nicardipine in the short-term therapy of light/moderate arterial hypertension].

This trial was designed to confirm the hypotensive action and safety of slow-release nicardipine, as a single drug or together with other hypotensive drugs, for the short-term treatment of mild-to-moderate hypertension, on a large case list of patients in 57 centers throughout Italy. A total of 1011 patients (502 M, 509 F) were admitted, mean age 58.6 +/- 9.1 years (range 25-87), mean weight 72.7 +/- 11.1 kg (range 43-128), with essential (972 cases) or secondary hypertension (39 cases). Nicardipine was given orally at a mean daily dosage of 80 mg (range 40-120), for four weeks. Clinically and statistically significant reductions in systolic and diastolic BP were observed at the end of treatment, with no noteworthy changes in heart rate. Nicardipine single-drug therapy restored normal blood pressure in 79.7% of patients with essential hypertension, and in 72.0% of those with secondary hypertension; nicardipine associated with other hypotensive agents achieved normal blood pressure in respectively 65.9% and 42.9%. Blood pressure returned to normal in 77.3% of patients with essential hypertension aged 65 years or under, and in 66.9% of those over 65 years old. These figures were respectively 70.8% and 46.7% for patients with secondary hypertension. The treatment was very well tolerated by 86.2% of patients; 140 (13.8%) presented adverse reactions, requiring dose reductions in 12, and discontinuation of treatment only in 24 cases. Five patients taking nicardipine together with another drug presented adverse reactions. These results confirm that slow-release nicardipine is effective and extremely well tolerated in the treatment of mild-to-moderate essential or secondary hypertension, in adults and the elderly.

Adult↗